One in Ten CD8+ Cells in the Pancreas of Living Individuals With Recent-Onset Type 1 Diabetes Recognizes the Preproinsulin Epitope PPI15-24

In type 1 diabetes (T1D), a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8⁺ T cells are the main cell type found in the insulitic lesion, and CD8⁺ T cells reactive against β-cell antigens have been detected in peripheral blood and in the pancreas of patients with short- or long-term disease. In the Diabetes Virus Detection (DiViD) study, researchers collected pancreatic tissue, by pancreatic tail resection, from living patients with recent-onset T1D. These tissues have been extensively studied by the scientific community, but the autoreactive nature of the T-cell infiltrate has remained unexplored. Our objective was to determine the number and localization of these cells in pancreas samples obtained through the DiViD study. Here, we demonstrate the presence of high frequencies of CD8⁺ T cells reactive against a highly relevant epitope derived from the preproinsulin signal peptide in pancreatic tissue samples from these donors. We also show the heterogeneity of islet distribution and CD8⁺ T-cell infiltration. Our findings contribute to the current limited existing knowledge of T-cell reactivity in the pancreas of donors with recent-onset T1D and indicate that antigen-specific therapies directed toward preproinsulin could have high clinical impact.     

Pediatric versus adult paradigms for management of adolescent injuries within a regional trauma system

BackgroundWe aimed to examine process and outcome indicators for adolescents with specific injury patterns managed in pediatric versus adult paradigms within the same trauma system.MethodsAdolescents (15–17 years old) admitted to the region's adult trauma center (ATC) or pediatric trauma center (PTC) with an abdominal injury, femur fracture or traumatic brain injury (TBI) were reviewed retrospectively. Global and injury-specific process and outcome indicators were compared.ResultsOf 141 ATC and 69 PTC patients, injury patterns differed significantly with more TBI and abdominal injuries at the ATC and femur fractures at the PTC. Overall injury severity was greater at the ATC. Patients with solid organ injuries appeared more likely to undergo embolization or splenectomy at the ATC; however, higher injury grade and later time period were the only variables significantly associated with this. Computed tomography (CT) was used significantly more frequently at the ATC overall, most notable with panscanning and head CTs for major TBI. Time to operative management did not differ for patients with isolated femur fractures. Neuropsychological follow up after minor TBI was documented more often at the PTC than the ATC; there was no difference for those with more severe TBIs.ConclusionsManagement varies for adolescents between PTCs and ATCs with more exposure to radiation and less neuropsychological follow-up of less severe TBIs at the ATC. This presents distinct opportunities to identify best policies for triage and sharing of management practices within a single regional inclusive trauma system in order to optimize short and long-term outcomes for this population.Type of studyRetrospective cohort.Level of evidenceLevel IV.     

Dexmedetomidine versus propofol for prolonged sedation in critically ill trauma and surgical patients

Backgroundand Purpose: Currently, dexmedetomidine versus propofol has primarily been studied in medical and cardiac surgery patients with outcomes indicating safe and effective sedation. The purpose of this study was to assess the efficacy of dexmedetomidine versus propofol for prolonged sedation in trauma and surgical patients.MethodsThis was a single-center prospective study conducted in the Trauma/Surgical Intensive Care Unit (ICU) at a Level I academic trauma center. It included patients 18 years of age or older requiring mechanical ventilation who were randomly assigned based on unit bed location to receive either dexmedetomidine or propofol. The primary outcome was duration of mechanical ventilation. Secondary outcomes included mortality; proportion of time in target sedation; incidence of delirium, hypotension, and bradycardia; and ICU and hospital length of stay (LOS).ResultsA total of 57 patients were included. Baseline characteristics were similar between groups. There was no significant difference in duration of mechanical ventilation (median [IQR]) between the dexmedetomidine (78.5[125] hours) and propofol (105[130] hours; p = 0.15) groups. There was no difference between groups in ICU mortality, ICU and hospital LOS, or incidence of delirium. Safety outcomes were also similar. Patients in the dexmedetomidine group spent a significantly greater percentage of time in target sedation (98[8] %) compared to propofol group (92[10] %; p = 0.02).ConclusionsOur results suggest that, similar to medical and cardiac surgery patients, dexmedetomidine and propofol are safe and effective sedation agents in critically ill trauma and surgical patients; however, dexmedetomidine achieves target sedation better than propofol for this specific population.     

External validity of phase III trials on vaccines against SARS-CoV-2 to a middle-aged and elderly Western European population

European Journal of Epidemiology - Initial results from various phase-III trials on vaccines against SARS-CoV-2 are promising. For proper translation of these results to clinical guidelines, it is...     

Adverse childhood experiences and the development of Down syndrome regression disorder

Down syndrome regression disorder (DSRD) is a clinical symptom cluster of acute or subacute neurocognitive regression in otherwise health persons with Down syndrome. The objective of this study was to evaluate if adverse childhood experiences (ACEs) were more prevalent in children with DSRD than those with DS alone. A survey-based, cohort-based study was performed. Caregivers of individuals with DSRD with onset of symptoms between age 10 and 30 years and DS alone were administered the ACEs questionnaire via an online REDCap survey. A total of 159 responses were collected after excluding incomplete surveys and those not meeting criteria for DSRD. Individuals with DSRD were not more likely to experience ACEs (p = 0.18, 95% confidence interval [CI]: 0.43–1.17). In those with ACEs prior to the onset of symptoms, the median time prior was 7 months (interquartile range: 5–10). Individuals with DSRD were more likely to report three or more ACEs (52, 33%) compared to those with DS alone (39, 22%) (p = 0.02, 95% CI: 1.08–2.87). Exposure to ACEs were not predictive of response to particular therapeutic interventions although those with multiple ACEs 3 months prior to the onset of symptoms was associated with lower response rates to benzodiazepines and immunotherapy (p = 0.02, 95% CI: −3.64–−1.13). This study provides preliminary data that individuals with DSRD experience ACEs at a similar rate to individuals with only DS alone, although three or more ACEs, often preceding the onset of symptoms, was more prevalent in individuals with DSRD.     

Relations between traumatic brain injury and the environment: feedback reduces maladaptive behaviour exhibited by three persons with traumatic brain injury

Feedback is a commonly used technique in neurorehabilitation. It functions to strengthen or weaken select relations between individuals' behaviour and their environment. The study of behaviour-environment relations is a focus of operant psychology, commonly referred to as behaviour analysis. Central to behaviour analysis is the analysis of interrelations among stimuli, behaviour, and consequences. The focus on behaviour-environment relations may have considerable benefits for designing clinical treatments and accounting for successful and unsuccessful treatments, especially psychological interventions for maladaptive behaviour. In the present investigation, three persons with traumatic brain injuries, diagnosed with depression and presenting mild cognitive impairments, received feedback about their maladaptive behaviour. Weekly feedback resulted in general reductions in the variability and frequency of maladaptive behaviour. The results support the utility of giving equal consideration to relations between persons with traumatic brain inury and their environment, despite existing psychological or cognitive impairments. Future research on variables that influence the development and maintenance of behaviour-environment relations, and more generally operant behaviour, may provide a unique perspective on the effects of traumatic brain injury.     

Adenosine coronary vasodilation quantitative technetium 99m methoxy isobutyl isonitrile myocardial tomography in the identification and localization of coronary artery disease

Background

Exercise and dipyridamole ^99mTc-labeled methoxy isobutyl isonitrile (MIBI) myocardial scintigraphy have been widely used for the diagnosis of coronary artery disease (CAD). However, only limited data on adenosine ^99mTc-labeled MIBI cardiac imaging are currently available. This study was designed to assess the accuracy of quantitative adenosinerest ^99mTc-labeled MIBI tomography in the diagnosis and localization of CAD.

Methods and Results

Fifty-seven consecutive patients with suspected CAD who underwent coronary angiography and 22 normal volunteers were studied. All patients underwent ^99mTc-labeled MIBI tomography after administration of adenosine (140 μg/kg intravenously for 6 minutes) and at rest. A total of 171 vascular coronary territories were analyzed quantitatively. All patients with CAD (≥50% luminal stenosis) (n=55) had abnormal ^99mTc-labeled MIBI tomograms. The normalcy rate was 86% by quantitative analysis. Overall sensitivity, specificity, and diagnostic accuracy for detection of individual stenosed vessels were 84%, 87%, and 85%, respectively. In patients with one-vessel CAD (n=24), sensitivity and diagnostic accuracy in the detection of individual stenosed vessels were significantly (p<0.05) higher compared with patients with multivessel CAD (n=31). Moreover, 75% of patients with one-vessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in only one coronary artery territory, and 74% of patients with multivessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in two or more coronary artery territories. Sensitivity, specificity, and diagnostic accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=18) compared with those with previous myocardial infarction (n=39). In myocardial territories related to noninfarcted areas (n=124), sensitivity and specificity in the detection of stenosed vessels were 75% and 88%. In infarcted areas (n=47), sensitivity and specificity in the detection of stenosed vessels were 98% and 80% (differences not significant vs noninfarcted areas).

Conclusions

Adenosine-controlled coronary vasodilation combined with quantitative ^99mTc-labeled MIBI tomography is accurate for identifying patients with CAD and localizing individual stenosed coronary arteries.